Background Tuberculosis (TB) incidence is consistently higher in men than women globally. Whether this disparity arises from differential infection risk or sex-specific rates of progression from infection to disease remains unclear. We evaluated sex differences in the development of TB disease while accounting for baseline infection status. Methods We conducted a pooled individual participant data analysis of 11 prospective cohort studies (n = 22,424), conducted between 2005 and 2017 across Sub-Saharan Africa, Europe, Asia, and South America. TB infection was defined by a positive QuantiFERON-TB Gold In-Tube result, and incident TB was defined by bacteriologically confirmed or clinical diagnosis. We used mixed-effects logistic and Cox proportional hazards models, adjusted for age, to estimate odds ratios (OR) for infection and hazard ratios (HR) for incident TB by sex. Findings Participants were followed for a median of 2.8 years, during which 411 individuals (1.8%) developed TB. Most participants were from Europe (52%) or South Africa/Zambia (34.4%). At baseline, males had a significantly higher likelihood of infection (OR 1.12; 95% CI 1.02–1.22). Among those with baseline infection, pooled incidence rates were 16.3 per 1000 person-years (95% CI 10.9–24.4) in females and 15.6 (95% CI 9.8–24.8) in males. The risk of developing TB did not differ by sex among those with baseline infection (HR 0.86; 95% CI 0.65–1.14) or without baseline infection (HR 1.02; 95% CI 0.71–1.47). Interpretation In these cohorts, males had a higher prevalence of baseline TB infection, but no clear excess risk of subsequent TB disease after accounting for baseline infection status. These findings suggest that sex differences in TB infection risk may contribute more to higher TB incidence among males than differences in TB disease risk after infection. Funding None.

Background:Misclassification of HIV status in population-based surveys remains a critical barrier to accurate surveillance and program evaluation. Self-reported HIV status may diverge from objective measures, particularly among individuals receiving antiretroviral therapy (ART). We used biomarker-confirmed antiretroviral (ARV) drug detection to assess the prevalence and correlates of discordance between self-reported HIV status and biologic evidence of HIV treatment among people living with HIV (PLHIV) in Zambia and South Africa. Methods:We conducted a secondary analysis of the HPTN 071 (PopART) cluster-randomized trial. At the 24-month survey visit, participants underwent HIV testing and laboratory assessment for ARV drugs in plasma. We defined discordant self-report (hereafter "non-disclosure") as reporting HIV-negative or unknown status among individuals with ARV drugs detected. We estimated the prevalence of non-disclosure, compared prevalence by study arm, and used modified Poisson regression to identify associated factors. We also examined whether non-disclosure was associated with viral suppression (<400 copies/mL). Results:Among 3,240 PLHIV with ARV drugs detected, 552 (17.0%) did not report an HIV-positive status-indicating that nearly one in six individuals on ART were misclassified by self-report. Non-disclosure did not differ between intervention and control arms (adjusted relative risk [aRR]: 1.03; 95% CI: 0.67-1.58). Non-disclosure was more common among younger individuals (age 18-24 years: aRR 2.30; 95% CI: 1.66-3.19), men (aRR: 1.39; 95% CI: 1.07-1.79), and those in formal employment (aRR: 1.42; 95% CI: 1.06-1.90). Individuals reporting condomless sex at last encounter were also more likely not to disclose (aRR: 1.59; 95% CI: 1.31-1.92). Viral suppression was high overall (93.7%) and did not differ by disclosure status (aRR: 1.06; 95% CI: 0.74-1.52). Conclusion:A substantial proportion of PLHIV receiving ART did not report a known HIV-positive status, highlighting important discordance between biomarker evidence and self-reported data. Despite high levels of viral suppression, these individuals remain "hidden" from routine surveillance, with implications for estimating HIV diagnosis and treatment coverage. Strategies that incorporate objective measures alongside self-report, and that address social and structural barriers to disclosure, are essential to improve the accuracy of HIV surveillance and guide effective public health responses.

Background:The World Health Organization-endorsed Xpert MTB/XDR assay provides a rapid method to detect resistance to isoniazid, fluoroquinolones, injectables aminoglycosides and ethionamide, yet evaluation of its performance, particularly in endemic settings, remains limited. Methods:We conducted a prospective multicentre study (June 2017 to March 2021) in nine sub-Saharan African countries, enrolling adults with pulmonary tuberculosis confirmed by Xpert MTB/RIF or Ultra. Xpert MTB/XDR results were compared to a World Health Organization-endorsed targeted next-generation sequencing reference used on the same sputum, with discordance resolved using whole genome sequencing and phenotypic drug-susceptibility testing when available. Diagnostic accuracy for each drug was calculated, also accounting for genotypic heteroresistance detection. Results:Among 1238 included patients, Xpert MTB/XDR demonstrated high specificity (≥98%) across all drugs yet showed variable sensitivity, detecting 606 out of 637 isoniazid-resistant (95%, 95% CI 94-97%), 22 out of 33 fluoroquinolones-resistant (67%, 95% CI 48-81%) and 159 out of 279 ethionamide-resistant (57%, 95% CI 51-63%) samples. The assay reliably detected most common resistance-conferring mutations, such as katG_S315T, fabG1_C-15T, and gyrA_A90V and D94G, yet failed to detect low-frequency heteroresistance (≤10-35%) and off-target mutations, mostly for ethionamide. Amikacin resistance was rare (0.2%). Sensitivity for fluoroquinolones was higher (78%) among rifampicin-resistant samples, highlighting its utility as a reflex test in rifampicin-resistant patients. Conclusions:Xpert MTB/XDR offers rapid diagnosis of resistance with high specificity. While limitations in detecting low-frequency and off-target variants affect its sensitivity, most frequent, fixed in-target mutations are readily detected. Future studies should evaluate strategies to integrate Xpert MTB/XDR with other diagnostic approaches in national tuberculosis programmes.

Migrants have been identified as a population left behind by the AIDS (Acquired Immune Deficiency Syndrome) response, with evidence showing poorer HIV (Human Immunodeficiency Virus) outcomes and reduced intervention effectiveness in mobile populations. We used data from the HPTN 071 (PopART) trial (ClinicalTrials.gov number, NCT01900977) to investigate migration and HIV-related indicators, assessing whether community migration influenced PopART trial results and whether migration was associated with HIV status and position on the care continuum. The PopART trial, conducted in Zambia and South Africa (SA) from November 2013 to June 2018, evaluated a universal testing and treatment intervention using a three-arm design. A cohort of 18-44-year-olds was followed annually to estimate HIV incidence, with migration out of trial communities tracked using this cohort. migration into and within the community was tracked using intervention delivery data in community members aged 18 + . HIV-related indicators were HIV status, knowledge of HIV-positive status and ART use. Migration's influence on the trial HIV incidence results was analysed using a two-stage approach for cluster-randomised trials, adjusting for community-level migration. Associations between HIV-related indicators and both out-migration (Poisson regression using cohort data) and in-migration (logistic regression using cross-sectional data) were also estimated. While migration differed between trial arms, there was no evidence that it confounded the intervention effect on HIV incidence. There was evidence out-migration was higher among HIV-positive individuals who did not know (or did not disclose) their HIV-positive status compared to those HIV-negative (adjusted rate ratio: Zambia 1.28, 95%CI 1.17-1.39; SA 1.27, 95%CI 1.17-1.38). Residents who had moved into the community within the previous year were less likely to be aware of their HIV-positive status than longer-term residents (adjusted odds ratio: Zambia 0.18, 95%CI 0.16-0.19; SA 0.23, 95%CI 0.20-0.28) and contributed to approximately one in four of the newly identified HIV infections. Following intervention delivery the gap in knowledge of HIV status and ART treatment coverage between recent in-migrants and longer-term residents closed. Countries with high HIV burden should aim to ensure a sustained delivery of HIV services in areas with high levels of population mobility and in areas with moderate to high HIV prevalence.

Abstract While much progress has been made in reducing the incidence of HIV-1 infection in sub-Saharan Africa in recent years, bringing the epidemic to an end will require identification of the demographic groups that continue to contribute to transmission. Pathogen phylogenetics and individual-based mathematical models (IBMs) of transmission are approaches that enable researchers to explore such questions. Here, we used both methods to characterise the ages and sexes of the individuals involved in heterosexual transmission in the context of the HPTN 071 (PopART) trial in Zambia. The results were concordant, and show that the male partner was on average older than the female by less than seven years, with larger age gaps in male-to-female than female-to-male transmissions. We found that the largest gaps for female recipients were amongst the youngest of those recipients. Conversely, the youngest male recipients saw the smallest gaps. We further used the IBM to demonstrate that transmission to new age cohorts first entering into sexual activity is driven predominantly by male-to-female transmission. We also simulated the PopART universal testing and treatment intervention into the future to show that effective treatment of under-35-year-olds accounts for 93.8% of the reduction in incidence by 2039, while effective treatment of under-35-year-old men accounts for 62.1%. Finally, we simulated a one-year cessation of ART treatment for the whole population, which resulted in an immediate increase in the average age at transmission of both sources and recipients. With it becoming ever more expensive and difficult to find treatment-naive individuals and link them to care, targeted interventions for demographic groups such as under-35 men may be the key to finally ending HIV.

Background:Herpes simplex virus type 2 (HSV2) is an important cofactor for HIV acquisition and transmission. Associations between the infections are reexamined in longitudinal data from an HIV prevention trial. Methods:The HPTN 071 (PopART) trial evaluated a combination prevention intervention in 21 urban communities in Zambia and South Africa. HIV incidence was measured in a cohort of approximately 2000 adults (age, 18-44 years) selected randomly from each community and followed up for 36 months. Incidence of HSV2 infection was estimated, and the effects of risk factors were examined. The association between HIV incidence and HSV2 infection was examined at individual and community levels. Results:An overall 10 539 participants were HSV2 negative at baseline and retested after 36 months. Estimated HSV2 incidence was 5.4 per 100 person-years (95% CI, 5.0-5.7) for women and 2.9 per 100 person-years (95% CI, 2.6-3.2) for men. When compared with those remaining HSV2 negative, HIV incidence was higher in those who were HSV2 positive at baseline (women: adjusted rate ratio [aRR], 3.24 [95% CI, 2.50-4.20]; men: aRR, 2.57 [95% CI, 1.60-4.11]) and even higher in those who seroconverted to HSV2 during follow-up (women: aRR, 5.94 [95% CI, 4.42-7.98]; men: aRR, 8.37 [95% CI, 5.18-13.52]). At the community level, strong associations were seen between HIV incidence and HSV2 prevalence (R 2 = 0.48, P < .001) and incidence (R 2 = 0.36, P = .004). Conclusions:There were strong associations between HIV incidence and HSV2 prevalence and incidence at individual and community levels. HSV2 control could contribute to HIV prevention.

In Sub-Saharan Africa, unmet need for contraceptives often remains high among adolescent girls and young women (AGYW), leading to unintended pregnancies. Yathu Yathu, a cluster-randomised trial of a community-based intervention conducted in two communities in Lusaka, Zambia (2019–2021), aimed to provide sexual and reproductive health services, including contraceptive services, to adolescents and young people. The trial showed no impact on pregnancy related outcomes. Hence, this analysis examined the characteristics of AGYW aged 15–24 with an unmet need for modern contraceptives and who experienced an unintended pregnancy. We also explored access to and reach of contraceptive services through Yathu Yathu. Secondary analysis of Yathu Yathu endline survey data. Using logistic regression, adjusted for cluster, we explored factors associated with unmet need for modern contraceptives and unintended pregnancies among AGYW in the intervention arm and assessed whether these associations differed in the control arm. Using routinely collected service delivery data from the intervention arm, numbers of AGYW accessing hormonal contraceptive services were described by age, community, educational attainment, and marital status. In the intervention arm, 395 AGYW ever had sex. Unmet need for modern contraceptives was 40.6 https://clinicaltrials.gov/ct2/show/NCT04060420 ; and ISRCTN75609016. Registration date: 2019-08-12.

OBJECTIVE:We investigate the risk of acquiring HIV or herpes simplex virus type 2 (HSV-2) among young women who sell sex (YWSS) in rural South Africa. DESIGN:A representative population-based prospective cohort study of adolescent girls and young women (AGYW). METHODS:Between 2017 and 2019, we interviewed a random sample of AGYW (13-30 years) annually and collected dried blood spot (DBS) samples for HIV and HSV-2 serology. YWSS were defined as engaging in transactional sex and/or sex work in the past 12 months. We used Cox regression to estimate the association between selling sex and incident HIV or HSV-2 infections, using inverse probability weighting to adjust for potential confounding (age, education, rural/urban locality, socioeconomic status (SES), food insecurity, and pregnancy status). RESULTS:Among eligible AGYW ( n  = 3846), 89.2% provided responses for at least one follow-up time-point, of whom 17% reported selling sex in the past 12 months. HIV and HSV-2 prevalence at enrolment were 21 and 37.9%, respectively and higher among YWSS at 42 and 69%, respectively. HIV incidence was 3.4/100 person-years [95% confidence interval (CI): 2.6-4.2] higher among YWSS than others (8.2 vs. 2.7/100 person-years; hazard ratio: 2.70; 95% CI: 1.83-3.99). HSV-2 incidence was 18.4/100 person-years (95% CI: 16.5-20.5), and was higher among YWSS than others (29.3 vs. 17.2/100 person-years; hazard ratio 1.83; 95% CI: 1.41-2.39). HSV-2 at baseline was associated with subsequent HIV infection (hazard ratio 6.32; 95% CI: 3.86-10.47, P  < 0.001). CONCLUSION:HIV and HSV-2 incidence was higher among AGYW selling sex compared those who did not sell sex. These findings highlight the need for preexposure prophylaxis (PrEP) and socioeconomic support for this priority population of AGYW in rural settings.

Comprehensive intervention packages are recommended to address multiple sources of HIV risk for adolescent girls and young women (AGYW). DREAMS is a multi-component HIV prevention program designed to reduce HIV incidence among AGYW. We conducted a prospective cohort study among AGYW aged 13-22 years, randomly selected in rural Gem and urban Nairobi informal settlements followed from 2017/2018-2019. AGYW were classified into three groups: (1) invited to DREAMS and received a "complete" package, (2) invited and received a "partial" package, or (3) not invited to DREAMS. We defined the "complete" package as 4-5 primary interventions in Gem and 5 in Nairobi: the "partial" package as 3 specific interventions in Gem and any 3-4 interventions in Nairobi. We used propensity score-adjusted logistic regression to estimate the causal effect of DREAMS on outcomes under three counterfactual scenarios: all AGYW accessed the complete package, all accessed a partial package, or none were invited. In Nairobi, 1081 AGYW were enrolled. By 2019, 26% accessed the complete package and 32% accessed the partial package. Among those receiving the complete package, there was increase in HIV status knowledge(24.8% [95%CI:16.4,32.6]),social support(13.9% [95%CI:3.3,23.6]) and self-efficacy(10.3% [95%CI:0.5,20.4]) and a decrease in the proportion with ≥2 lifetime partners(-8.0% [95%CI:-15.9,0.0]). In Gem, 1171 AGYW were enrolled. By 2019, 24% received the complete package and 21% received the partial package. We found evidence of an increase in HIV status knowledge(10.0% [95%CI:4.5,15.2]), social support(27.2% [95%CI:19.2,35.5]) and a decrease in condomless sex(-9.1% [95%CI:-13.6,-4.1]), and the proportion with ≥2 lifetime partners(-7.6% [95%CI:-12.4,-2.2]) for the complete package. Among those receiving the partial package, there was a decrease in condomless sex(-12.2% [95%CI: -17.0,-6.4]), and an increase in self-efficacy(8.0% [95%CI:0.0,17]). A package of 4-5 primary DREAMS interventions had positive impacts on multiple HIV-related outcomes in both settings. A partial package was effective in Gem, but not in Nairobi, suggesting the need for context-specific intervention strategies.

Menstrual cups could be a sustainable menstrual material for adolescent girls and young women (AGYW) in sub-Saharan Africa. Yathu Yathu was a cluster-randomized trial of community-based delivery of HIV and sexual and reproductive health services to young people in Lusaka, Zambia. Among services available through the intervention were menstrual products, including menstrual cups. We explored knowledge of menstruation and menstrual products, acceptability, and experiences of using cups among AGYW aged 15–24. We share lessons learned on how to distribute cups through community-based strategies to AGYW in urban communities. Through community-based, peer-led spaces (hubs), AGYW could access menstrual products, including pads and menstrual cups. We conducted four focus group discussions, two with AGYW aged 15–19 (n = 9) and 20–21 (n = 8) who had accessed different menstrual products through Yathu Yathu and two with AGYW aged 15–19 (n = 5) and 20–24 (n = 9) who had accessed menstrual cups. Four interviews were conducted with four AGYW (15–19, n = 2; 20–24, n = 2) who had accessed cups, and four with two AGYW who were enrolled in a qualitative cohort. Data were analyzed thematically. ‘Surprise’ and ‘fear’ were initial reactions from most AGYW who saw the cups for the first time at Yathu Yathu hubs. Misconceptions that cups cause cancer and fears that they could get stuck in the vagina, cause sore, vagina enlargement, and loss of virginity were raised by AGYW. The desire to try the cup, use an alternative menstrual product and information gained at the hubs facilitated access. Use of the cup was comfortable, and cups were said to be cost-effective and durable. Advantages over pads included: the absence of odor, easy to maintain, and environmentally friendly: “it is hygienic, and it is even easy to maintain”. Challenges included pain, discomfort, and failure to or incorrectly inserting the cup at initial use. When faced with challenges using the cup, AGYW reported going back to the hub for additional information and demonstrations on use. Despite concerns, misconceptions and initial challenges, cups were acceptable among AGYW. Free distribution of cups provides an opportunity to address menstrual health challenges among AGYW. However, as a new product, there is need to increase awareness and provide detailed information on use.

TRIAL REGISTRATION:ClinicalTrials.gov NCT01900977.

OBJECTIVES:We conducted a pilot time location sampling survey with young men aged 20-35 years in Lusaka, Zambia and aimed to describe knowledge of HIV status and determine factors associated with knowledge of HIV status. METHODS:Hotspots where men congregate were identified in a densely populated community in Lusaka. Hotspots were grouped into five strata (betting shops; car parks/washes; bus stations/taxi ranks; churches; and markets/shopping streets) and day/times when hotspots were frequented by men were listed. Within each stratum, three hotspots were randomly selected. Subsequently, 1 day/time was randomly selected for each hotspot. Men aged 20-35 were approached for participation and data was collected between July and October 2022. We describe participation in the survey, socio-demographics, and sexual behaviours. Using logistic regression, we explored factors associated with knowledge of HIV status. RESULTS:339 men were approached, among whom 304 (90%) were eligible and 297 (98%) consenting to participate. Overall, 61% knew their HIV status. Adjusting for recruitment strata, knowledge of HIV status was similar by age (20-24: 56%; 25-29: 68%; and 30-35: 55%; p = 0.19). Among men reporting sex in the last month, men reporting no condomless sex were more likely to know their HIV status (78.2%) compared to men reporting one condomless sex partner in the past 1 month (55.5%; age-adjusted OR = 3.02; 95%CI 1.07, 8.55; p = 0.07). Knowledge of HIV status was lower among men who thought their friends were testing every 2-5 years (48%; n = 12/29) compared to those assuming that their friends tested more frequently (70.0%; adjOR = 0.28; 95%CI 0.08, 0.98; p < 0.001). CONCLUSION:The time location sampling survey was acceptable among men, as evidenced by high participation. Overall, 40% of young men did not know their HIV status. A hotspot-driven approach to delivering HIV testing services may prove effective at reaching men. Furthermore, time location sampling surveys should be explored as a tool to evaluate interventions targeting men.

Background The World Health Organization suggest that systematic tuberculosis (TB) screening may be conducted in high prevalence settings (>0.5%), though supporting evidence is limited. Methods Between January-2014 to December-2017, the HPTN 071 (PopART) cluster-randomized trial implemented universal HIV and TB testing across 21 communities in Zambia and South Africa (SA), with TB prevalence of 0.5% and 1.6%, respectively. Trained community health workers visited households annually to offer HIV testing and TB symptom screening, with sputum collection from individuals who screened positive. Diagnostic testing used Xpert-MTB/RIF or smear microscopy, and linkage to treatment was facilitated. We analysed TB screening and diagnosis data across three rounds (R1–R3) in Zambia and R3 in SA, where complete data were available. We examined factors associated with reporting TB symptoms and being diagnosed with TB. Results The yield of newly diagnosed TB (per 100,000 persons) increased across rounds in Zambia [R1 = 81, R2 = 93, R3 = 110; p-value (trend) = 0.003] and was higher in R3 SA (380). In R3, TB yield was higher in men (Zambia: 146; SA: 543) than women (Zambia: 76; SA: 257), and among newly diagnosed HIV-positive individuals (Zambia: 541; SA: 789) compared to HIV-negative individuals (Zambia: 48; SA: 170) and self-reported HIV-positive individuals on ART (Zambia: 105; SA: 192). In Zambia R3, participants screened twice before had 38% lower odds of being diagnosed with TB compared to those screened first time [Adjusted odds ratio = 0.62, 95% CI (0.43, 0.90)]. Conclusion The PopART intervention identified undiagnosed TB through systematic TB symptom screening, particularly in men and newly diagnosed HIV-positive individuals and individuals who had not previously been screened. Yield was relatively low compared to estimated TB prevalence. Trial registration [ClinicalTrials.gov][1] NCT01900977 ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT01900977 ### Funding Statement This work was supported by the National Institute of Allergy and Infectious Diseases, the US President’s Emergency Plan for AIDS Relief, the International Initiative for Impact Evaluation, the Bill and Melinda Gates Foundation, the National Institute on Drug Abuse, and the National Institute of Mental Health. The content herein is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the ethics committees of the London School of Hygiene & Tropical Medicine, the University of Zambia, and Stellenbosch University. Additional Institutional Review Board approvals were given for including those aged 15 years and older in later rounds. Individuals gave informed verbal consent to participate in the intervention and informed written or witnessed consent for HIV testing. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes We will provide aggregate data sufficient to replicate the main analyses presented in this paper. These aggregate data will include counts of tuberculosis screening and diagnostic outcomes stratified by country, round, trial arm, community, gender, age group, HIV status, and participation in previous screening rounds. The protocol approved by the ethics committees specifies that intervention data can only be shared in aggregate form. For queries related to these data, the PI of the HPTN Statistical Data Management Centre (SDMC), Deborah Donnell (deborah{at}scharp.org), can be contacted. [1]: http://ClinicalTrials.gov

Like in many countries, coverage of sexual and reproductive health (SRH) services among adolescents and young people (AYP) aged 15–24 remains low in Zambia. Increasing coverage of SRH services requires interventions that are responsive to the needs and preferences of AYP. We conducted a discrete choice experiment (DCE) to elicit AYP’s preferences for SRH service delivery in Lusaka, Zambia. A cross-sectional DCE was conducted with AYP aged 15–24 years. Consenting participants were presented with alternative SRH service delivery strategies represented by six attributes, namely: location, type of provider, type of services, service differentiation by sex, availability of edutainment, and opening hours. Multinomial logit and random parameters logit models were used to analyse the data. All variables were effect coded. A total of 423 AYP aged 15–24 years (61

Empowerment is key to person-centered HIV prevention. This study aims to evaluate the extent to which the Determined, Resilient, Empowered, AIDS-free, Mentored, Safe (DREAMS) Partnership promotes empowerment of adolescent girls and young women (AGYW) in Kenya. We conducted a mixed-methods study to examine DREAMS influence on empowerment precursors (resources, agency, institutional structures) and outcomes, guided by Kabeer's framework for women's empowerment. With representative cohorts of AGYW aged 13-22, followed since 2017/18, we estimated the impact of DREAMS on social support and self-efficacy by 2022. With a nested sample of cohort participants in 2022, we conducted qualitative inquiry through in-depth interviews and participatory action learning with DREAMS participants, implementers, and community members, for evidence of mechanisms, achievement and contextual influences on AGYW empowerment. We found statistical evidence of a causal impact of DREAMS on social support and self-efficacy among adolescent girls. Qualitatively, DREAMS enhanced AGYW's access to and control of resources, including coveted material assets like educational subsidies, hygiene products, and business support, which reportedly reduced transactional sex through economic autonomy and bodily integrity. DREAMS enhanced intangible resources like HIV knowledge and financial skills. Greater confidence, courage, and critical consciousness enabled some AGYW to act on health choices, assume leadership roles, and continue education. In mentor-led activities, AGYW demonstrated collective action and solidarity and group saving skills for financial autonomy. DREAMS aimed to engage the broader community including leaders, parents, and young men, but social structures, dominant gender norms, gender-based violence, and widespread poverty mitigated its empowering impact for AGYW. We found compelling evidence that DREAMS strengthened many young women's access to and control of resources and their intrinsic and collective agency. These are important precursors to empowerment but insufficient for the transformation of power relations without supportive institutional structures, including gender-equitable norms and viable livelihood strategies.

HPTN 071 (PopART) implemented a comprehensive HIV prevention package which aimed to reduce HIV incidence within 21 communities of Zambia and South Africa: Arm A, PopART intervention of universal HIV testing and treatment; Arm B, PopART intervention of universal HIV testing with ART provided according to local guidelines; and Arm C, standard of care. Analyses so far have not accounted for the sampling design of the enrolled cohort. We performed a sample-weighted re-analysis of the primary outcome of the PopART trial to derive a population-based estimate of the intervention effect. Enrollment used a two-stage sampling design: household and adult participant within each household. We constructed post-stratification weights to match the age and sex distribution of the target population in these communities. Weighted Poisson regression was used to estimate community-level HIV incidence. The PopART intervention effect was estimated using log-transformed community-level incidence estimates in an ANCOVA model. The analysis based on community-level incidence shows a 25

WHO recommends computer-aided detection (CAD) in chest X-ray (CXR) for systematic screening of TB. Increased detection of individuals with high CAD score but without bacteriologically confirmed TB can be expected, requiring guidance on their clinical management. We followed participants of a TB prevalence survey (TBPS) in Zambia and South Africa with a high CAD score but no bacteriologically confirmed TB over a median time of 9 months and assessed their clinical outcomes. At the TBPS participants with TB-suggestive symptoms or a CAD score ≥40 submitted two sputum samples for Xpert-Ultra testing, and, an additional sample was collected the next day for liquid culture and Xpert-ultra testing. Participants with a CAD score ≥70 and no bacteriologically confirmed TB were eligible for follow-up. At follow-up visit participants were asked about TB symptoms and treatment, underwent a repeat CXR with CAD, and those with either TB-suggestive symptoms or a CAD score ≥70 at follow-up submitted a sputum sample for Xpert-Ultra testing. A composite "clinical" outcome was defined based on changes in CAD-score and TB-suggestive symptoms between the TBPS and the follow-up. Of the 254 eligible TBPS participants 162 (65%) completed follow-up. Most of the participants self-reported previous TB (65% 105/162), were from Zambia (79%, 128/162,) and male (70%, 97/162). Overall, 43% (70/162) participants progressed clinically/remained radiologically abnormal and 6% (10/162) developed TB between the TBPS and the follow-up, with an overall TB incidence rate of 7% per year (95% CI: 3.8-13.3). Patients with high CAD score but no bacteriological confirmation may have had a past TB or other pulmonary lesions identified in the CXR, which may need to be investigated. Also, these participants may be at risk of progressing to TB over time and could benefit from a follow-up visit and from repeated assessment of symptoms and CXR.

Combination HIV prevention packages have reduced HIV incidence and improved HIV-related outcomes among young people. However, there is limited data on how package components interact to promote HIV-related prevention behaviours. We described the uptake of HIV prevention interventions supported by Determined, Resilient, Empowered, AIDS-free, Motivated and Safe (DREAMS) Partnership and assessed the association between uptake and HIV-related behaviours among young people in rural KwaZulu-Natal, South Africa. We analysed two cohorts followed from May 2017 to December 2019 to evaluate the impact of DREAMS, covering 13-29 year-old females, and 13-35 year-old males. DREAMS interventions were categorised as healthcare-based or social. We described the uptake of interventions and ran logistic regression models to investigate the association between intervention uptake and subsequent protective HIV-related outcomes including no condomless sex and voluntary medical male circumcision (VMMC). For each outcome, we adjusted for socio-demographics and sexual/pregnancy history and reported adjusted odds ratios (aOR) and 95% confidence intervals (CI). Among 5248 participants, uptake of healthcare interventions increased from 2018 to 2019 by 8.1% and 3.7% for males and females respectively; about half of participants reported receiving both healthcare and social interventions each year. The most utilised combinations of interventions included HIV testing and counselling, school-based HIV education and cash transfers. Participation in social interventions only compared to no intervention was associated with reduced condomless sex (aOR = 1.60, 95%CI: 1.03-2.47), while participation in healthcare interventions only was associated with increased condomless sex. The uptake of interventions did not significantly affect subsequent VMMC overall. Among adolescent boys, exposure to school-based HIV education, cash transfers and HIV testing and counselling was associated with increase in VMMC (aOR = 1.79, 95%CI: 1.04-3.07). Multi-level HIV prevention interventions were associated with an increase in protective HIV-related behaviours emphasizing the importance of accessible programs within both school and community settings for young people.